Session 9 Flashcards
What diseases can cardiovascular drugs be used to treat?
Arrhythmias, heart failure, angina, hypertension and risk of thrombus formation.
What are the possible causes of arrhythmias?
Ectopic pacemaker activity - damaged area of myocardium becomes depolarised and spontaneously active or a latent pacemaker region is activated due to ischaemia.
After depolarisations - abnormal depolarisations following AP due to high intracellular Ca2+. Leads to a longer QT interval.
Re entry loop - unidirectional block setting up a circuit of excitation. Several small re entry loops can lead to AF.
What are the four main classes of anti-arrythmic drugs?
Class I - drugs that block voltage gated Na+ channels
Class 2 - antagonists of B-adrenoreceptors (B-blockers)
Class 3 - K+ channel blockers
Class 4 - Ca2+ channel blockers
Describe how class I anti-arrhythmic drugs work
E.g. The local anaesthetic lidocaine. They block voltage gated Na+ channels in the open or inactive state (use dependent) and dissociate rapidly ready for the next action potential.
Lidocaine blocks the damaged areas of myocardium from depolarising (prevents the firing of APs too close to each other).
Describe how class II anti-arrhythmic drugs work
E.g. Propranolol. Act on B1 adrenoreceptors in the heart to block sympathetic action. Decrease slope of pacemaker potential. They can be used following an MI (which causes increased sympathetic activity) to prevent ventricular arrhythmias and to reduce the O2 demand (reduces myocardial ischaemia).
They also slow conduction in the AV node to treat patients with AF.
Describe how class III anti-arrhythmic drugs work
They prolong the action potential by blocking K+ channels, lengthening the absolute refractory period and preventing an AP occurring too soon. Rarely used because they can be pro-arrhythmic!
Amiodarone has other actions in addition to blocking K+ channels and is used to treat tachycardia associated with Wolf-Parkinson White syndrome (re entry loop due to extra conduction pathway between atria and ventricles).
Describe how class IV anti-arrhythmic drugs work
E.g. Verapamil. Decreases slope of pacemaker AP at SA node, decreases AV node conduction and decreases force of contraction. Also causes some coronary and peripheral vasodilation.
How does adenosine prevent arrhythmias from developing?
Acts on “A1” receptors (not alpha 1) at the AV node to enhance K+ conductance (hyper polarising cells).
What are the two broad mechanisms of actions for drugs used to treat heart failure and what drugs achieve this?
Positive ionotropes that increase cardiac output - cardiac glycosides and B adrenoreceptor agonist
Drugs which reduce the workload of the heart - ACE inhibitors, B-blockers and diuretics.
Describe the mechanism of action of cardiac glycosides in treating heart failure
They block Na+/K+ ATPase, leading to an increase in intracellular Na+. This reduces the activity of NCX, increasing intracellular Ca2+ and increasing force of contraction.
Describe the mechanism of action of B-adrenoreceptor agonists in treating heart failure
E.g. Dobutamine. They increase myocardial contractility hence they increase cardiac output.
Describe the mechanism of action of ACE inhibitors in treating heart failure
They inhibit the action of angiotensin converting enzyme preventing angiotensin I -> angiotensin II. Angiotensin II normally acts on the kidneys to increase Na+ and water reabsorption and is a vasoconstrictor. ACE inhibitors therefore reduces the afterload (decreases BP) and preload (decreases blood volume) of the heart.
What are the two broad mechanisms of actions for drugs used to treat angina and what drugs achieve this?
Reducing the work load of the heart - B blockers, Ca2+ channel antagonists and organic nitrates
Improving coronary blood supply - organic nitrates, Ca2+ channel antagonists
What is the mechanism of action of organic nitrates on the cardiovascular system?
They produce NO which is a powerful vasodilator through activation of guanylate cyclase.
Their primary action is the venous system which lowers the preload, reducing the workload of the heart and decreasing it’s O2 demand (used for angina).
Their secondary action is on the coronary arteries, improving O2 delivery to ischaemic myocardium.
What cardiovascular conditions can increase the risk of thrombus formation?
Atrial fibrillation, acute MI and prosthetic heart valves
